4-[[(3S)-3-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]-4-oxo-4-[[(2R)-1-oxo-3-[4-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]-1-piperidin-1-ylpropan-2-yl]amino]butanoyl]amino]butanoic acid | 343776-74-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 4-[[(3S)-3-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]-4-oxo-4-[[(2R)-1-oxo-3-[4-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]-1-piperidin-1-ylpropan-2-yl]amino]butanoyl]amino]butanoic acid
• CAS: 343776-74-9
• 化学式: C₃₄H₄₄N₆O₁₀S
• 分子量: 728.824
• InChiKey: YGLQFAMFYHGJIZ-IZZNHLLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  51
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  230
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  4-[[(3S)-3-[(4-methoxy-2,3,6-trimethylphenyl)sulfonylamino]-4-oxo-4-[[(2R)-1-oxo-3-[4-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]-1-piperidin-1-ylpropan-2-yl]amino]butanoyl]amino]butanoic acid 、 五氟苯酚 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以87%的产率得到4-[4-[[(1R)-1-[[4-(1,2,4-oxadiazol-5(2H)-one)-phenyl]methyl]-2-oxo-2-(1-piperidinyl) ethyl]amino]-3-[[(4-methoxy-2,3,6-trimethylphenyl)sulfonyl]amino]-1,4(S)-dioxobutyl] amino-butanoic acid pentafluorophenyl ester
  参考文献：
  名称：

  Synthesis of a stable-isotope-labeled biotinylated pentasaccharide conjugate (EP217609), a dual-effect anticoagulant drug

  摘要：

  EP217609 是一种可中和的双效抗凝剂，目前正在心脏手术心肺旁路中进行临床研究。我们合成了稳定同位素标记的 EP217609，作为支持生物测定的质谱内标。EP217609 由三个结构单元经六个步骤合成，总收率为 42%，化学纯度大于 99%。因此，首先在由[13C,15N]-l-赖氨酸 2 分三步制备的 N 保护标记生物素-赖氨酸 4 和五糖-间隔胺 6 之间进行偶联。去除 8 上的 Cbz 保护基团，然后与活化的肽模拟构筑基块 10 相耦合，就得到了 EP217609 的直接前体，它可以在 1,2,4-噁二唑-5(2H)-酮催化氢解成脒后得到。

  DOI：

  10.1002/jlcr.1900

文献信息

• ANTITHROMBOTIC COMPOUND
  申请人：Merck Sharp & Dohme B.V.

  公开号：EP1237897B1

  公开（公告）日：2015-01-14
• Antithrombotic Dual Inhibitors Comprising A Biotin Residue
  申请人：De Kort Martin

  公开号：US20100004186A1

  公开（公告）日：2010-01-07

  The present invention relates compounds of the formula (I) oligosaccharide-spacer-A (1), wherein the oligosaccharide is a negatively charged oligosaccharide residue comprising two to twenty five monosaccharide units, the charge being compensated by positively charged counterions, and wherein the oligosaccharide residue is derived from an oligosaccharide which has (AT-III mediated) anti-Xa activity per se; the spacer is an essentially pharmacologically inactive flexible linking residue having a chain length of 10 to 70 atoms; A is the residue —CH[NH—SO 2 —R 1 ][CO—NR 2 —CH(4-benzamidine)-CO—NR 3 R 4 ], wherein R1 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (iso)quinolinyl, tetrahydro(iso)quinolinyl, 3,4-dihydro-1H-isoquinolinyl, chromanyl or the camphor group, which groups may optionally be substituted with one or more substituents selected from (1-8C)alkyl or (1-8C)alkoxy; and wherein R 2 and R 3 are independently H or (1-8C)alkyl; R 4 is (−8C)alkyl or (3-8C)cycloalkyl; or R 3 and R 4 together with the nitrogen atom to which they are bonded are a nonaromatic (4-8) membered ring optionally containing another heteroatom, the ring optionally being substituted with (1-8C)alkyl or SO2-(1-8C)alkyl; or a pharmaceutically acceptable salt thereof a prodrug or solvate thereof; wherein the compound of formula I further comprises at least one covalent bond with a biotin residue or an analogue thereof. The compounds of the invention have antithrombotic activity and can be used in treating or preventing thrombosis or other thrombin-related diseases. The antithrombotic activity of the compound of this invention can be neutralized in case of emergency upon administration of avidin, streptavidin and analogues thereof having high biotin affinity.
• ANTITHROMBOTIC DUAL INHIBITORS COMPRISING A BIOTIN RESIDUE
  申请人：DE KORT Martin

  公开号：US20120245109A1

  公开（公告）日：2012-09-27

  The present invention relates compounds of the formula (I) oligosaccharide-spacer-A   (I), wherein the oligosaccharide is a negatively charged oligosaccharide residue comprising two to twenty five monosaccharide units, the charge being compensated by positively charged counterions, and wherein the oligosaccharide residue is derived from an oligosaccharide which has (AT-III mediated) anti-Xa activity per se; the spacer is an essentially pharmacologically inactive flexible linking residue having a chain length of 10 to 70 atoms; A is the residue —CH[NH—SO 2 —R 1 ][CO—NR 2 —CH(4-benzamidine)-CO—NR 3 R 4 ], wherein R 1 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, (iso)quinolinyl, tetrahydro(iso)quinolinyl, 3,4-dihydro-1H-isoquinolinyl, chromanyl or the camphor group, which groups may optionally be substituted with one or more substituents selected from (1-8C)alkyl or (1-8C)alkoxy; and wherein R 2 and R 3 are independently H or (1-8C)alkyl; R 4 is (1-8C)alkyl or (3-8C)cycloalkyl; or R 3 and R 4 together with the nitrogen atom to which they are bonded are a nonaromatic (4-8)membered ring optionally containing another heteroatom, the ring optionally being substituted with (1-8C)alkyl or SO 2 -(1-8C)alkyl; or a pharmaceutically acceptable salt thereof a prodrug or solvate thereof; wherein the compound of formula I further comprises at least one covalent bond with a biotin residue or an analogue thereof. The compounds of the invention have antithrombotic activity and can be used in treating or preventing thrombosis or other thrombin-related diseases. The antithrombotic activity of the compound of this invention can be neutralized in case of emergency upon adminstration of avidin, streptavidin and analogues thereof having high biotin affinity.
• US8445450B2
  申请人：——

  公开号：US8445450B2

  公开（公告）日：2013-05-21
• US8729307B2
  申请人：——

  公开号：US8729307B2

  公开（公告）日：2014-05-20